Testosterone in Metastatic Renal Cell Carcinoma Patients

Metastatic Renal Cell Carcinoma Clinical Trial

— FARETES  

Official title:

Phase 2 Randomized Study of Efficacy and Safety of Testosterone in Metastatic Renal Cell Carcinoma Patients With Fatigue

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03379012
• Other study ID #: KCRB08022016
• Status: Completed
• Phase: Phase 2
• Start date: February 8, 2016
• Est. completion date: July 30, 2019

Study information

• Verified date: October 2019
• Source: Kidney Cancer Research Bureau
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose

To determine efficacy and safety of Testosterone in male patients with metastatic renal cell carcinoma and fatigue receiving targeted therapy or checkpoint inhibitors.

Description:

Fatigue is a frequent symptom of metastatic renal cell carcinoma (RCC), and most common adverse event of targeted and immunotherapy.

In Phase 3 pivotal studies, 56% (9%, grade 3-4), 54% (11%, grade 3), 37% (10%, grade 3-4) and 20% (2%, grade 3) of patients had fatigue during the therapy of cabozantinib, sunitinib, axitinib or pazopanib, respectively. 59% (14%, grade 3) and 31% (5%, grade 3) of patients treated with lenvatinib/everolimus and everolimus had fatigue in registrational trials. Finally, 33% (2%, grade 3-4) of patients that received nivolumab had fatigue in CheckMate 025 study.

Testosterone may help to relieve fatigue associated with the use of tyrosine kinase, mTOR or checkpoint inhibitors. Additionally, testosterone could impact on poor prognostic factors of RCC (anemia, ECOG performance status, serum calcium). This will be first clinical trial which evaluates safety and efficacy of Testosterone in RCC patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 30, 2019
• Est. primary completion date: January 30, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically proven clear cell renal cell carcinoma;

2. CT-confirmed metastatic measurable disease;

3. First-line sunitinib or pazopanib treatment with fatigue;

4. Low level of testosterone;

4. Male, 18 years and older; 5. Normal PSA level

Exclusion Criteria:

1. Prostate and other cancers history

2. Hypothyroidism

3. History of serious cardiac arrhythmia, congestive heart failure, angina pectoris, or other severe cardiovascular disease (i.e., New York Heart Association class III or IV)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

Intervention

Drug:
• Testosterone undecanoate and sunitinib or pazopanib
Testosterone undecanoate (Nebido®) 1,000 mg (4 ml) intramuscular deeply, once before targeted therapy (sunitinib 50 mg 4/2 or pazopanib 800 mg daily)

Locations

Country	Name	City	State
Russian Federation	A.I. Kryzhanovsky Krasnoyarsk Cancer Center	Krasnoyarsk
Russian Federation	Kidney Cancer Research Bureau	Moscow
Russian Federation	RUDN University	Moscow
Russian Federation	City Clinical Oncology Center	Saint Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
Kidney Cancer Research Bureau

Country where clinical trial is conducted

Russian Federation, 

References & Publications (7)

Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3. Epub 2016 Jun 5. — View Citation

Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. doi: 10.1002/cncr.25219. — View Citation

Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. doi: 10.1016/S1470-2045(13)70093-7. Epub 2013 Apr 16. Erratum in: Lancet Oncol. 2013 Jun;14(7):e254. — View Citation

Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-1482. doi: 10.1016/S1470-2045(15)00290-9. Epub 2015 Oct 22. Erratum in: Lancet Oncol. 2016 Jul;17 (7):e270. Lancet Oncol. 2018 Oct;19(10):e509. — View Citation

Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. — View Citation

Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12. — View Citation

Tomita Y, Fukasawa S, Shinohara N, Kitamura H, Oya M, Eto M, Tanabe K, Kimura G, Yonese J, Yao M, Motzer RJ, Uemura H, McHenry MB, Berghorn E, Ozono S. Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup analysis from the CheckMate 025 study. Jpn J Clin Oncol. 2017 Jul 1;47(7):639-646. doi: 10.1093/jjco/hyx049. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fatigue	Difference in mean change of Fatigue from baseline score with testosterone vs. without testosterone.	3 months
Secondary	Safety and tolerability	Safety and tolerability of testosterone (CTCAE v.4.03)	3 months
Secondary	Quality of life	Health-related quality of life (NCCN-FACT FKSI-19 (Version 2)	3 months
Secondary	Overall rate of adverse events	Overall rate of adverse events related with TKI treatment (CTCAE v.4.03)	3 months
Secondary	Testosterone serum concentrations	Maximum and minimum total testosterone serum concentrations following dose administration at week 12	12 weeks
Secondary	Red blood cell count and Hemoglobin concentration	Change in Red blood cell count and Hemoglobin concentration following dose administration at week 12	12 weeks
Secondary	Serum calcium concentration	Change in serum calcium concentration following dose administration at week 12	12 weeks
Secondary	ECOG PS	ECOG Performance status	3 months
Secondary	Overall survival	Time from randomization to death	2 years